Methadone is a Schedule II drug best known for its use in the treatment of opioid dependence. Dental providers should be aware of the oral and systemic effects of methadone. In patients undergoing methadone maintenance therapy, there is a higher incidence of rampant caries, xerostomia, bruxism and poor oral hygiene. A review of the pharmacology, systemic effects, drug interactions and oral manifestations is presented, as well as possible modifications to treatment and specific considerations in dental therapies.